Dendrimeric support or carrier macromolecule

• US 7,097,856 B2
• Filed: 09/25/2001
• Issued: 08/29/2006
• Est. Priority Date: 09/29/2000
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Frechet, Jean J., Ihre, Rolf H.
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US09/963,858
• Publication Number:
  US 20020123609A1
• Time in Patent Office: 1,799 Days
• Field of Search: 424/486, 514/772, 549/370, 528/272, 536/23.1
• US Class Current: 424/486
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: C08G 83/003 Dendrimers

Abstract

The present invention provides a family of dendrimers that are useful as supports, vectors, carriers or delivery vehicles for a variety of compounds in biomedical and technological applications. In particular, the macromolecules may be used for the delivery of drugs, genetic material, imaging components or other functional molecule to which they can be conjugated. An additional feature of the macromolecules is their ability to be targeted for certain organs, tumors, or types of tissues.

Claims

1. A composition of matter consisting essentially of a plurality of dendrimers, wherein said composition of matter comprises a subunit having the structure:

2. The composition of matter according to claim 1, wherein A is a component of a polymer.

3. The composition of matter according to claim 2, wherein said polymer is a member selected from the group consisting of nucleic acids, linear poly(alkylene oxides), star poly(alkylene oxides), polysaccharides, poly(amino acids) and poly(hydroxystyrene).

4. The composition of matter according to claim 3, wherein said polysaccharide is a member selected from cyclodextrin, starch, hydroxyethyl starch and dextran.

5. The composition of matter according to claim 3, wherein said poly(amino acid) comprises lysine, tyrosine, serine, cysteine, arginine, histidine and combinations thereof.

6. The composition of matter according to claim 2, wherein said polymer is a synthetic organic polymer with pendant NH groups, OH groups, SH groups and combinations thereof.

7. The composition of matter according to claim 6, wherein said synthetic organic polymer is a member selected from poly(vinylphenol), poly(hydroxymethacrylate), poly(N-2-hydroxypropylmethacrylamide), poly(diallylamine), poly(lactic acid) and poly(hydroxymethylcaprolactone), poly(4-hydroxyethylcaprolactone).

8. The composition of matter according to claim 1, wherein at least one of said R⁵ and R⁶ is a therapeutic agent, and wherein said therapeutic agent is a member selected from the group consisting of antiproliferative agents, proteins, anti-cancer chemotherapeutic agents, antibiotics, antivirals, and antiparasitics.

9. The composition of matter according to claim 1, wherein at least one of said R⁵ and R⁶ is a diagnostic agent, and wherein said diagnostic agent is a member selected from MRI contrast agents, X-ray contrast agents, CT contrast agents, PET contrast agents, ultrasonography contrast agents, fluorescent agents, chromophoric agents and radioisotopes.

10. The composition of matter according to claim 1, wherein said subunit repeats from 2 to 100 times.

11. The composition of matter according to claim 10, wherein said subunit repeats from 4 to 50 times.

12. The composition of matter according to claim 11, wherein said subunit repeats from 8 to 24 times.

13. The composition of matter according to claim 1, wherein at least one of R⁵ and R⁶ has the structure:

14. The composition of matter according to claim 1, wherein at least one of R⁵ and R⁶ has the structure:

15. The composition of matter according to claim 14, wherein R⁷ is a doxorubicin derivative.

16. A pharmaceutical formulation comprising the composition of matter according to claim 1 and a pharmaceutically acceptable carrier.

19. The composition of matter of claim 1, wherein said dendrimers are produced by a process comprising:

(a) forming a reaction mixture by contacting a core moiety comprising A with an acylating group in an organic solvent, said acylating group having the structure;

20. The composition of matter according to claim 19, wherein A is a component of a polymer.

21. The composition of matter according to claim 20, wherein said polymer is a member selected from the group consisting of nucleic acids, linear poly(alkylene oxides), star poly(alkylene oxides), polysaccharides, poly(amino acids) and poly(hydroxystyrene).

22. The composition of matter according to claim 19, wherein at least one of said R⁵ and R⁶ is a therapeutic agent, and wherein said therapeutic agent is a member selected from the group consisting of antiproliferative agents, proteins, anti-cancer chemotherapeutic agents, antibiotics, antivirals, and antiparasitics.

23. The composition of matter according to claim 19, wherein at least one of said R⁵ and R⁶ is a diagnostic agent, and wherein said diagnostic agent is a member selected from MRI contrast agents, X-ray contrast agents, CT contrast agents, PET contrast agents, ultrasonography contrast agents, fluorescent agents, chromophoric agents and radioisotopes.

24. The composition of matter according to claim 19, wherein said subunit repeats from 2 to 100 times.

25. The composition of matter according to claim 24, wherein said subunit repeats from 4 to 50 times.

26. The composition of matter according to claim 25, wherein said subunit repeats from 8 to 24 times.

27. The composition of matter according to claim 19, wherein at least one of R⁵ and R⁶ has the structure:

28. The composition of matter according to claim 19, wherein at least one of R⁵ and R⁶ has the structure:

29. The composition of matter according to claim 28, wherein R⁷ is a doxorubicin derivative.

30. A pharmaceutical formulation comprising the composition of matter according to claim 19 and a pharmaceutically acceptable carrier.

31. The composition of matter according to claim 19, produced by a process which further comprises:

(c) removing said diol protecting group, thereby forming a first generation dendrimer comprising a subunit having the structure;

32. A composition of matter consisting essentially of a plurality of dendrimers, wherein said composition of matter comprises a subunit having the structure:

33. The composition of matter according to claim 32, produced by a process which further comprises:

(c) removing said diol protecting group, thereby forming a second generation dendrimer comprising a subunit having the structure;

17. A composition of matter consisting essentially of a plurality of dendrimers, wherein said composition of matter comprises a subunit having the structure:

18. A composition of matter consisting essentially of a plurality of dendrimers, wherein said composition of matter comprises a subunit having the structure: